The proposal is intended to study the operation of polyol pathway in normal and diabetic human and other primate lens and retinal tissues. They will be examined for aldose reductase, polyol dehydrogenase, hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase, lactate dehydrogenase and the oxidized and reduced forms of the various pyridine nucleotides. The methods to be used in various phases of work are outlined in the description of the research proposal. The human tissues will be obtained postmortem as soon as possible after death. Ultrasonic studies will be conducted to examined if the myopia associated with diabetes can be offset by treatment with aldose reductase inhibitors. Such studies will be conducted primarily on monkeys and efforts will be made to carry on few experiments involving human beings in the future. The use of human patients thus does not constitute part of this program. In the case of retina, studies on polyol pathway will be extended to cultured mural cells as well as to the entire vasculature with a view to determining the possible role of aldose reductase in capillary dilatation and mural cell degeneration in diabetes. In view of the importance of aldose reductase inhibitors in studying the pathogenesis as well as prevention of diabetic manifestations purported to be initiated by polyol accumulation, efforts will be made to discover more potent inhibitors of aldose reductase amongst the flavonoids and related compounds and their pharmacokinetic properties studies following oral or subcutaneous feeding/administration.